The use of brain-specific biomarkers in urine for prediction of neurological outcome and extent of tissue damage following stroke

Abstract Serum biomarkers of neuronal and glial damage gained significant attention in recent years for their diagnostic and prognostic value in acute stroke. In this study, we explored the potential of spot urine testing as a practical, non-invasive alternative. Using ultrasensitive single-molecule arrays, we assessed levels of glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and total tau (t-tau) in urine and blood samples from hospitalized patients with acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) within 96 h after symptom onset. The results were correlated with mortality rates, tissue damage extent and modified Rankin Scale (mRS) scores at discharge and after three months. Significant variables were included into an multivariate regression model with confounder correction (NIHSS at admission, age at onset and serum creatinine). As a result, absolute concentrations of urine GFAP, NfL and t-tau were significantly higher in patients with in-hospital death or death at 3 months follow-up compared to patients reaching a mRS ≤ 3. Using multivariate regressions models, urine GFAP demonstrated the strongest predictive value across all biomarkers for in-hospital functional outcome, which was superior to the respective GFAP serum concentrations, whereas NfL in serum was the only significantly predictive biomarker for 3 months functional outcome. For radiological outcomes, urine GFAP concentrations were closely linked with ischemic lesion size (ρ = 0.42, p = 0.01). In conclusion, the measurement of neuronal and glial biomarkers in urine is feasible and may enhance the prediction of functional and imaging outcomes.